NO123855B - - Google Patents
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- Publication number
- NO123855B NO123855B NO4913/68A NO491368A NO123855B NO 123855 B NO123855 B NO 123855B NO 4913/68 A NO4913/68 A NO 4913/68A NO 491368 A NO491368 A NO 491368A NO 123855 B NO123855 B NO 123855B
- Authority
- NO
- Norway
- Prior art keywords
- acid
- indole
- chloro
- formula
- phenyl
- Prior art date
Links
- -1 1-substituted benzodiazepine Chemical class 0.000 claims description 52
- 238000000034 method Methods 0.000 claims description 47
- 150000001875 compounds Chemical class 0.000 claims description 25
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 150000003839 salts Chemical class 0.000 claims description 17
- 238000006243 chemical reaction Methods 0.000 claims description 16
- 239000007800 oxidant agent Substances 0.000 claims description 10
- 229940053197 benzodiazepine derivative antiepileptics Drugs 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000005843 halogen group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 3
- 229910052739 hydrogen Inorganic materials 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- 125000004573 morpholin-4-yl group Chemical class N1(CCOCC1)* 0.000 claims description 2
- 229910052757 nitrogen Inorganic materials 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 54
- 239000000203 mixture Substances 0.000 description 42
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
- 238000002844 melting Methods 0.000 description 39
- 230000008018 melting Effects 0.000 description 39
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 31
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 26
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 24
- 239000000243 solution Substances 0.000 description 23
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- 239000002904 solvent Substances 0.000 description 16
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- 238000001816 cooling Methods 0.000 description 15
- 238000006722 reduction reaction Methods 0.000 description 15
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 14
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
- 239000002244 precipitate Substances 0.000 description 13
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 12
- 239000011541 reaction mixture Substances 0.000 description 12
- 238000001953 recrystallisation Methods 0.000 description 12
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 12
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 11
- 239000002253 acid Substances 0.000 description 11
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 11
- 239000012044 organic layer Substances 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- CBTITARLOCZPDU-UHFFFAOYSA-N 1h-indole-2-carbonitrile Chemical class C1=CC=C2NC(C#N)=CC2=C1 CBTITARLOCZPDU-UHFFFAOYSA-N 0.000 description 10
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 10
- 229960000583 acetic acid Drugs 0.000 description 10
- 235000011054 acetic acid Nutrition 0.000 description 10
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 239000012280 lithium aluminium hydride Substances 0.000 description 10
- 239000011976 maleic acid Substances 0.000 description 10
- 229940098895 maleic acid Drugs 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 9
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- RNAODKZCUVVPEN-UHFFFAOYSA-N 1h-indol-2-ylmethanamine Chemical class C1=CC=C2NC(CN)=CC2=C1 RNAODKZCUVVPEN-UHFFFAOYSA-N 0.000 description 8
- LWFZLPUSRONGSO-UHFFFAOYSA-N 5-chloro-3-(2-fluorophenyl)-1h-indole-2-carbonitrile Chemical compound FC1=CC=CC=C1C1=C(C#N)NC2=CC=C(Cl)C=C12 LWFZLPUSRONGSO-UHFFFAOYSA-N 0.000 description 8
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 8
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 150000001414 amino alcohols Chemical class 0.000 description 8
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 8
- 239000000460 chlorine Substances 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- 229910052938 sodium sulfate Inorganic materials 0.000 description 8
- 235000011152 sodium sulphate Nutrition 0.000 description 8
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 7
- 150000001557 benzodiazepines Chemical class 0.000 description 7
- 229940013688 formic acid Drugs 0.000 description 7
- 235000019253 formic acid Nutrition 0.000 description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- 229910052783 alkali metal Inorganic materials 0.000 description 6
- 239000000538 analytical sample Substances 0.000 description 6
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 239000005457 ice water Substances 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 6
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 5
- KRVSOGSZCMJSLX-UHFFFAOYSA-L chromic acid Substances O[Cr](O)(=O)=O KRVSOGSZCMJSLX-UHFFFAOYSA-L 0.000 description 5
- 125000004093 cyano group Chemical group *C#N 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- AWJWCTOOIBYHON-UHFFFAOYSA-N furo[3,4-b]pyrazine-5,7-dione Chemical compound C1=CN=C2C(=O)OC(=O)C2=N1 AWJWCTOOIBYHON-UHFFFAOYSA-N 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 150000007524 organic acids Chemical class 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- YQRMTKYDBUKFNE-UHFFFAOYSA-N 5-chloro-1-[2-(diethylamino)ethyl]-3-(2-fluorophenyl)indole-2-carboxamide Chemical compound C(C)N(CCN1C(=C(C2=CC(=CC=C12)Cl)C1=C(C=CC=C1)F)C(=O)N)CC YQRMTKYDBUKFNE-UHFFFAOYSA-N 0.000 description 4
- ZSUGHPOZDXFEJZ-UHFFFAOYSA-N 5-chloro-3-(2-fluorophenyl)-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F ZSUGHPOZDXFEJZ-UHFFFAOYSA-N 0.000 description 4
- ASGAHGHLFFGPBN-UHFFFAOYSA-N 5-chloro-3-phenyl-1h-indole-2-carboxamide Chemical compound NC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 ASGAHGHLFFGPBN-UHFFFAOYSA-N 0.000 description 4
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 4
- 229910015900 BF3 Inorganic materials 0.000 description 4
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 4
- 150000007513 acids Chemical class 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 4
- 229910021529 ammonia Inorganic materials 0.000 description 4
- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- 238000004821 distillation Methods 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 238000001228 spectrum Methods 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 description 3
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- 239000005711 Benzoic acid Substances 0.000 description 3
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
- CBENFWSGALASAD-UHFFFAOYSA-N Ozone Chemical compound [O-][O+]=O CBENFWSGALASAD-UHFFFAOYSA-N 0.000 description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 3
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 235000010233 benzoic acid Nutrition 0.000 description 3
- 229960004365 benzoic acid Drugs 0.000 description 3
- SXDBWCPKPHAZSM-UHFFFAOYSA-N bromic acid Chemical compound OBr(=O)=O SXDBWCPKPHAZSM-UHFFFAOYSA-N 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 229960004106 citric acid Drugs 0.000 description 3
- 235000015165 citric acid Nutrition 0.000 description 3
- 238000009833 condensation Methods 0.000 description 3
- 230000005494 condensation Effects 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 239000001530 fumaric acid Substances 0.000 description 3
- 229960002598 fumaric acid Drugs 0.000 description 3
- 235000011087 fumaric acid Nutrition 0.000 description 3
- 229940093915 gynecological organic acid Drugs 0.000 description 3
- 150000002500 ions Chemical class 0.000 description 3
- BTNMPGBKDVTSJY-UHFFFAOYSA-N keto-phenylpyruvic acid Chemical class OC(=O)C(=O)CC1=CC=CC=C1 BTNMPGBKDVTSJY-UHFFFAOYSA-N 0.000 description 3
- 239000004310 lactic acid Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 229960000448 lactic acid Drugs 0.000 description 3
- 239000001630 malic acid Substances 0.000 description 3
- 235000011090 malic acid Nutrition 0.000 description 3
- 229940099690 malic acid Drugs 0.000 description 3
- 229960002510 mandelic acid Drugs 0.000 description 3
- 229910052987 metal hydride Inorganic materials 0.000 description 3
- 150000004681 metal hydrides Chemical class 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 235000005985 organic acids Nutrition 0.000 description 3
- 229940116315 oxalic acid Drugs 0.000 description 3
- 235000006408 oxalic acid Nutrition 0.000 description 3
- 230000003647 oxidation Effects 0.000 description 3
- 238000007254 oxidation reaction Methods 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 3
- OXNIZHLAWKMVMX-UHFFFAOYSA-N picric acid Chemical compound OC1=C([N+]([O-])=O)C=C([N+]([O-])=O)C=C1[N+]([O-])=O OXNIZHLAWKMVMX-UHFFFAOYSA-N 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 229960004889 salicylic acid Drugs 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000011975 tartaric acid Substances 0.000 description 3
- 229960001367 tartaric acid Drugs 0.000 description 3
- 235000002906 tartaric acid Nutrition 0.000 description 3
- 229950002929 trinitrophenol Drugs 0.000 description 3
- UDLAUVFRZXIQJS-UHFFFAOYSA-N 1,3-dihydro-1,4-benzodiazepin-2-one Chemical class N1C(=O)CN=CC2=CC=CC=C21 UDLAUVFRZXIQJS-UHFFFAOYSA-N 0.000 description 2
- WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 2
- QSNSCYSYFYORTR-UHFFFAOYSA-N 4-chloroaniline Chemical compound NC1=CC=C(Cl)C=C1 QSNSCYSYFYORTR-UHFFFAOYSA-N 0.000 description 2
- IMUZPCJSWNBMLL-UHFFFAOYSA-N 5-chloro-3-phenyl-1h-indole-2-carbonitrile Chemical compound C12=CC(Cl)=CC=C2NC(C#N)=C1C1=CC=CC=C1 IMUZPCJSWNBMLL-UHFFFAOYSA-N 0.000 description 2
- YVZLRMZSZPZZSS-UHFFFAOYSA-N 5-chloro-3-phenyl-1h-indole-2-carbonyl chloride Chemical compound ClC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 YVZLRMZSZPZZSS-UHFFFAOYSA-N 0.000 description 2
- YPHLYLTWLDQJPX-UHFFFAOYSA-N 5-nitro-3-phenyl-1H-indole-2-carboxamide Chemical compound [N+](=O)([O-])C=1C=C2C(=C(NC2=CC1)C(=O)N)C1=CC=CC=C1 YPHLYLTWLDQJPX-UHFFFAOYSA-N 0.000 description 2
- DSWVTYMKIQJSLM-UHFFFAOYSA-N 5-nitro-3-phenyl-1h-indole-2-carbonitrile Chemical compound C12=CC([N+](=O)[O-])=CC=C2NC(C#N)=C1C1=CC=CC=C1 DSWVTYMKIQJSLM-UHFFFAOYSA-N 0.000 description 2
- BMZNTPXQZKYUKD-UHFFFAOYSA-N 5-nitro-3-phenyl-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC=C([N+]([O-])=O)C=C2C=1C1=CC=CC=C1 BMZNTPXQZKYUKD-UHFFFAOYSA-N 0.000 description 2
- YXAVKKSHULKVJO-UHFFFAOYSA-N 7-chloro-3-(2-fluorophenyl)-1H-indole-2-carboxamide Chemical compound ClC=1C=CC=C2C(=C(NC12)C(=O)N)C1=C(C=CC=C1)F YXAVKKSHULKVJO-UHFFFAOYSA-N 0.000 description 2
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 2
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
- 239000012448 Lithium borohydride Substances 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 2
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 238000000862 absorption spectrum Methods 0.000 description 2
- 150000001340 alkali metals Chemical class 0.000 description 2
- 150000001342 alkaline earth metals Chemical class 0.000 description 2
- 150000001412 amines Chemical class 0.000 description 2
- 150000001735 carboxylic acids Chemical class 0.000 description 2
- 238000010531 catalytic reduction reaction Methods 0.000 description 2
- 150000001805 chlorine compounds Chemical class 0.000 description 2
- AFAXGSQYZLGZPG-UHFFFAOYSA-N ethanedisulfonic acid Chemical compound OS(=O)(=O)CCS(O)(=O)=O AFAXGSQYZLGZPG-UHFFFAOYSA-N 0.000 description 2
- BBERMKLZMWHBCY-UHFFFAOYSA-N ethyl 5-chloro-3-(2-fluorophenyl)-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F BBERMKLZMWHBCY-UHFFFAOYSA-N 0.000 description 2
- FSLOLRKVZPTMHC-UHFFFAOYSA-N ethyl 5-chloro-3-phenyl-1h-indole-2-carboxylate Chemical compound CCOC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 FSLOLRKVZPTMHC-UHFFFAOYSA-N 0.000 description 2
- 229960003750 ethyl chloride Drugs 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 150000004820 halides Chemical class 0.000 description 2
- 238000002329 infrared spectrum Methods 0.000 description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 2
- NUJOXMJBOLGQSY-UHFFFAOYSA-N manganese dioxide Chemical compound O=[Mn]=O NUJOXMJBOLGQSY-UHFFFAOYSA-N 0.000 description 2
- 229910017604 nitric acid Inorganic materials 0.000 description 2
- 150000002825 nitriles Chemical class 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 2
- 238000006049 ring expansion reaction Methods 0.000 description 2
- 239000000523 sample Substances 0.000 description 2
- 235000010288 sodium nitrite Nutrition 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- FFWQLZFIMNTUCZ-UHFFFAOYSA-N 1-(bromomethyl)-2-fluorobenzene Chemical compound FC1=CC=CC=C1CBr FFWQLZFIMNTUCZ-UHFFFAOYSA-N 0.000 description 1
- ZFFBIQMNKOJDJE-UHFFFAOYSA-N 2-bromo-1,2-diphenylethanone Chemical compound C=1C=CC=CC=1C(Br)C(=O)C1=CC=CC=C1 ZFFBIQMNKOJDJE-UHFFFAOYSA-N 0.000 description 1
- 239000001903 2-oxo-3-phenylpropanoic acid Substances 0.000 description 1
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 1
- NYYRRBOMNHUCLB-UHFFFAOYSA-N 3-chloro-n,n-dimethylpropan-1-amine Chemical compound CN(C)CCCCl NYYRRBOMNHUCLB-UHFFFAOYSA-N 0.000 description 1
- AZBKNDOQANAWNI-UHFFFAOYSA-N 3-phenyl-5-(trifluoromethyl)-1H-indole-2-carboxamide Chemical compound C1(=CC=CC=C1)C1=C(NC2=CC=C(C=C12)C(F)(F)F)C(=O)N AZBKNDOQANAWNI-UHFFFAOYSA-N 0.000 description 1
- KMVPXBDOWDXXEN-UHFFFAOYSA-N 4-nitrophenylhydrazine Chemical compound NNC1=CC=C([N+]([O-])=O)C=C1 KMVPXBDOWDXXEN-UHFFFAOYSA-N 0.000 description 1
- YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 1
- UCCNNQGKEBUQJY-UHFFFAOYSA-N 5-chloro-1-[2-(diethylamino)ethyl]-3-(2-fluorophenyl)indole-2-carbonitrile Chemical compound CCN(CC)CCn1c(C#N)c(-c2ccccc2F)c2cc(Cl)ccc12 UCCNNQGKEBUQJY-UHFFFAOYSA-N 0.000 description 1
- GWQFYINGOBLJRX-UHFFFAOYSA-N 5-chloro-3-(2-fluorophenyl)-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F GWQFYINGOBLJRX-UHFFFAOYSA-N 0.000 description 1
- WQRNPWUZAVBEBC-UHFFFAOYSA-N 5-chloro-3-phenyl-1h-indole-2-carboxylic acid Chemical compound OC(=O)C=1NC2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 WQRNPWUZAVBEBC-UHFFFAOYSA-N 0.000 description 1
- QVRZOWOMUACTBI-UHFFFAOYSA-N 5-methoxy-3-phenyl-1H-indole-2-carboxamide Chemical compound COC=1C=C2C(=C(NC2=CC1)C(=O)N)C1=CC=CC=C1 QVRZOWOMUACTBI-UHFFFAOYSA-N 0.000 description 1
- QLAONILSZQDWHJ-UHFFFAOYSA-N 5-methyl-3-phenyl-1H-indole-2-carboxamide Chemical compound CC=1C=C2C(=C(NC2=CC1)C(=O)N)C1=CC=CC=C1 QLAONILSZQDWHJ-UHFFFAOYSA-N 0.000 description 1
- QHNWTXJHPWAPMS-UHFFFAOYSA-N 7-chloro-1-[2-(diethylamino)ethyl]-5-phenyl-3h-1,4-benzodiazepin-2-one Chemical compound N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 QHNWTXJHPWAPMS-UHFFFAOYSA-N 0.000 description 1
- QUYLCUGBYNYTMQ-UHFFFAOYSA-N 7-chloro-1-[3-(diethylamino)propyl]-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-one;dihydrochloride Chemical compound Cl.Cl.N=1CC(=O)N(CCCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F QUYLCUGBYNYTMQ-UHFFFAOYSA-N 0.000 description 1
- JZHPERDCMWAKPD-UHFFFAOYSA-N 7-chloro-1-[3-(dimethylamino)propyl]-5-(2-fluorophenyl)-3h-1,4-benzodiazepin-2-one;dihydrochloride Chemical compound Cl.Cl.N=1CC(=O)N(CCCN(C)C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F JZHPERDCMWAKPD-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- IHFHTEQUTSSHTH-UHFFFAOYSA-N CCCC(=O)C(C(O)=O)CC1=CC=CC=C1 Chemical compound CCCC(=O)C(C(O)=O)CC1=CC=CC=C1 IHFHTEQUTSSHTH-UHFFFAOYSA-N 0.000 description 1
- BHHJXTWMSLJIOT-UHFFFAOYSA-N CN(C)CCCN1C2=CC=C(Cl)C=C2C(=C1C(N)=O)C1=C(F)C=CC=C1 Chemical compound CN(C)CCCN1C2=CC=C(Cl)C=C2C(=C1C(N)=O)C1=C(F)C=CC=C1 BHHJXTWMSLJIOT-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- ZIIJJOPLRSCQNX-UHFFFAOYSA-N Flurazepam hydrochloride Chemical compound Cl.Cl.N=1CC(=O)N(CCN(CC)CC)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1F ZIIJJOPLRSCQNX-UHFFFAOYSA-N 0.000 description 1
- LELOWRISYMNNSU-UHFFFAOYSA-N Hydrocyanic acid Natural products N#C LELOWRISYMNNSU-UHFFFAOYSA-N 0.000 description 1
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-M Methanesulfonate Chemical compound CS([O-])(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-M 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- WDNIVTZNAPEMHF-UHFFFAOYSA-N acetic acid;chromium Chemical compound [Cr].CC(O)=O.CC(O)=O WDNIVTZNAPEMHF-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 1
- 150000008046 alkali metal hydrides Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
- 230000002152 alkylating effect Effects 0.000 description 1
- DEDGUGJNLNLJSR-UHFFFAOYSA-N alpha-hydroxycinnamic acid Natural products OC(=O)C(O)=CC1=CC=CC=C1 DEDGUGJNLNLJSR-UHFFFAOYSA-N 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 description 1
- 229940125681 anticonvulsant agent Drugs 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 description 1
- 229940054051 antipsychotic indole derivative Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- CBHOOMGKXCMKIR-UHFFFAOYSA-N azane;methanol Chemical compound N.OC CBHOOMGKXCMKIR-UHFFFAOYSA-N 0.000 description 1
- 239000002585 base Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- IMNRJGSQCGFPHL-UHFFFAOYSA-N benzene;oxolane Chemical compound C1CCOC1.C1=CC=CC=C1 IMNRJGSQCGFPHL-UHFFFAOYSA-N 0.000 description 1
- CIZVQWNPBGYCGK-UHFFFAOYSA-N benzenediazonium Chemical class N#[N+]C1=CC=CC=C1 CIZVQWNPBGYCGK-UHFFFAOYSA-N 0.000 description 1
- 125000003310 benzodiazepinyl group Chemical group N1N=C(C=CC2=C1C=CC=C2)* 0.000 description 1
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 1
- HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 150000001649 bromium compounds Chemical class 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- BRPQOXSCLDDYGP-UHFFFAOYSA-N calcium oxide Chemical compound [O-2].[Ca+2] BRPQOXSCLDDYGP-UHFFFAOYSA-N 0.000 description 1
- 239000000292 calcium oxide Substances 0.000 description 1
- ODINCKMPIJJUCX-UHFFFAOYSA-N calcium oxide Inorganic materials [Ca]=O ODINCKMPIJJUCX-UHFFFAOYSA-N 0.000 description 1
- 229950005499 carbon tetrachloride Drugs 0.000 description 1
- 125000005392 carboxamide group Chemical group NC(=O)* 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- HRYZWHHZPQKTII-UHFFFAOYSA-N chloroethane Chemical compound CCCl HRYZWHHZPQKTII-UHFFFAOYSA-N 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000010908 decantation Methods 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- 239000012954 diazonium Substances 0.000 description 1
- 150000001989 diazonium salts Chemical class 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000000921 elemental analysis Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 239000003326 hypnotic agent Substances 0.000 description 1
- 230000000147 hypnotic effect Effects 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940035363 muscle relaxants Drugs 0.000 description 1
- 239000003158 myorelaxant agent Substances 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KVBGVZZKJNLNJU-UHFFFAOYSA-N naphthalene-2-sulfonic acid Chemical class C1=CC=CC2=CC(S(=O)(=O)O)=CC=C21 KVBGVZZKJNLNJU-UHFFFAOYSA-N 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229940127240 opiate Drugs 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 150000004965 peroxy acids Chemical class 0.000 description 1
- 150000004031 phenylhydrazines Chemical class 0.000 description 1
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 235000011056 potassium acetate Nutrition 0.000 description 1
- 239000012286 potassium permanganate Substances 0.000 description 1
- YLLIGHVCTUPGEH-UHFFFAOYSA-M potassium;ethanol;hydroxide Chemical compound [OH-].[K+].CCO YLLIGHVCTUPGEH-UHFFFAOYSA-M 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 235000012239 silicon dioxide Nutrition 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
- KSMWLICLECSXMI-UHFFFAOYSA-N sodium;benzene Chemical compound [Na+].C1=CC=[C-]C=C1 KSMWLICLECSXMI-UHFFFAOYSA-N 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- 125000001273 sulfonato group Chemical class [O-]S(*)(=O)=O 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-M toluene-4-sulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-M 0.000 description 1
- FAQYAMRNWDIXMY-UHFFFAOYSA-N trichloroborane Chemical compound ClB(Cl)Cl FAQYAMRNWDIXMY-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7890467 | 1967-12-08 | ||
| JP7890367 | 1967-12-08 | ||
| JP7916967 | 1967-12-09 | ||
| JP8227467 | 1967-12-21 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| NO123855B true NO123855B (enrdf_load_stackoverflow) | 1972-01-24 |
Family
ID=27466229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO4913/68A NO123855B (enrdf_load_stackoverflow) | 1967-12-08 | 1968-12-07 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US3632805A (enrdf_load_stackoverflow) |
| BE (1) | BE725159A (enrdf_load_stackoverflow) |
| CH (1) | CH529145A (enrdf_load_stackoverflow) |
| DE (1) | DE1812205C3 (enrdf_load_stackoverflow) |
| FI (1) | FI48839C (enrdf_load_stackoverflow) |
| FR (1) | FR1602150A (enrdf_load_stackoverflow) |
| GB (1) | GB1260479A (enrdf_load_stackoverflow) |
| IL (1) | IL31242A (enrdf_load_stackoverflow) |
| NL (1) | NL146814B (enrdf_load_stackoverflow) |
| NO (1) | NO123855B (enrdf_load_stackoverflow) |
| SE (1) | SE353327B (enrdf_load_stackoverflow) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3922264A (en) * | 1967-12-07 | 1975-11-25 | Sumitomo Chemical Co | Production of benzodiazepine derivatives |
| DE2617062C2 (de) * | 1976-04-17 | 1985-07-04 | Cassella Ag, 6000 Frankfurt | Wasserlösliche Hydrazone der Phthalocyaninreihe, ihre Herstellung und Verwendung |
| DE3807922A1 (de) * | 1988-03-10 | 1989-09-21 | Boehringer Mannheim Gmbh | Substituierte heterocyclen, verfahren zu ihrer herstellung sowie arzneimittel, die diese verbindungen enthalten |
| US20110104109A1 (en) * | 2005-07-13 | 2011-05-05 | Frank Bennett | Tetracyclic indole derivatives and their use for treating or preventing viral infections |
| JP5079818B2 (ja) | 2006-12-22 | 2012-11-21 | メルク・シャープ・アンド・ドーム・コーポレーション | Ｈｃｖおよび関連するウイルス疾患の治療または予防のための４，５−環インドール誘導体 |
| CN101611002A (zh) * | 2006-12-22 | 2009-12-23 | 先灵公司 | 用于治疗或预防hcv和相关病毒感染的4,5-环化吲哚衍生物 |
| WO2008136815A2 (en) | 2006-12-22 | 2008-11-13 | Schering Corporation | 5, 6-ring annulated indole derivatives and use thereof |
| DK2134685T3 (en) | 2007-04-16 | 2015-12-07 | Abbvie Inc | 7-unsubstituted indole derivatives as MCL-1 inhibitors |
| JP5272007B2 (ja) * | 2007-08-29 | 2013-08-28 | メルク・シャープ・アンド・ドーム・コーポレーション | ウイルス感染症を治療するための２，３−置換インドール誘導体 |
| CN101842374A (zh) * | 2007-08-29 | 2010-09-22 | 先灵公司 | 用于治疗病毒感染的2，3-取代的氮杂吲哚衍生物 |
| EP2408761B1 (en) * | 2007-08-29 | 2014-01-01 | Merck Sharp & Dohme Corp. | Substituted indole derivatives and methods of use thereof |
| EP2222672B1 (en) * | 2007-11-16 | 2013-12-18 | Merck Sharp & Dohme Corp. | 3-aminosulfonyl substituted indole derivatives and methods of use thereof |
| JP5249344B2 (ja) * | 2007-11-16 | 2013-07-31 | メルク・シャープ・アンド・ドーム・コーポレーション | ヘテロ環の３位が置換されたインドール誘導体およびその使用 |
| US8901139B2 (en) * | 2008-06-13 | 2014-12-02 | Merck Sharp & Dohme Corp. | Tricyclic indole derivatives and methods of use thereof |
-
1968
- 1968-11-29 US US780174A patent/US3632805A/en not_active Expired - Lifetime
- 1968-12-02 DE DE1812205A patent/DE1812205C3/de not_active Expired
- 1968-12-05 GB GB57773/68A patent/GB1260479A/en not_active Expired
- 1968-12-05 FI FI683496A patent/FI48839C/fi active
- 1968-12-05 NL NL686817433A patent/NL146814B/xx not_active IP Right Cessation
- 1968-12-06 CH CH1831768A patent/CH529145A/de not_active IP Right Cessation
- 1968-12-06 IL IL31242A patent/IL31242A/en unknown
- 1968-12-06 FR FR176996A patent/FR1602150A/fr not_active Expired
- 1968-12-07 NO NO4913/68A patent/NO123855B/no unknown
- 1968-12-09 BE BE725159A patent/BE725159A/xx not_active IP Right Cessation
- 1968-12-09 SE SE16832/68A patent/SE353327B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BE725159A (enrdf_load_stackoverflow) | 1969-05-16 |
| FI48839B (enrdf_load_stackoverflow) | 1974-09-30 |
| DE1812205C3 (de) | 1978-10-19 |
| FR1602150A (enrdf_load_stackoverflow) | 1970-10-12 |
| IL31242A0 (en) | 1969-02-27 |
| DE1812205B2 (de) | 1978-02-09 |
| DE1812205A1 (de) | 1969-07-03 |
| NL6817433A (enrdf_load_stackoverflow) | 1969-06-10 |
| GB1260479A (en) | 1972-01-19 |
| US3632805A (en) | 1972-01-04 |
| FI48839C (fi) | 1975-01-10 |
| CH529145A (de) | 1972-10-15 |
| IL31242A (en) | 1973-07-30 |
| NL146814B (nl) | 1975-08-15 |
| SE353327B (enrdf_load_stackoverflow) | 1973-01-29 |
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